Other articles by David H. Gracias on PubMed

We demonstrate the patterned assembly of integrated semiconductor devices onto planar, flexible, and curved substrates on the basis of capillary interactions involving liquid solder. The substrates presented patterned, solder-coated areas that acted both as receptors for the components of the device during its assembly and as electrical connections during its operation. The components were suspended in water and agitated gently. Minimization of the free energy of the solder-water interface provided the driving force for the assembly. One hundred and thirteen GaAlAs light-emitting diodes with a chip size of 280 micrometers were fabricated into a prototype cylindrical display. It was also possible to assemble 1500 silicon cubes, on an area of 5 square centimeters, in less than 3 minutes, with a defect rate of approximately 2%.

Proceedings of the National Academy of Sciences of the United States of America. Apr, 2002 | Pubmed ID: 11959945

This paper introduces a biomimetic strategy for the fabrication of asymmetrical, three-dimensional electronic devices modeled on the folding of a chain of polypeptide structural motifs into a globular protein. Millimeter-size polyhedra-patterned with logic devices, wires, and solder dots-were connected in a linear string by using flexible wire. On self-assembly, the string folded spontaneously into two domains: one functioned as a ring oscillator, and the other one as a shift register. This example demonstrates that biomimetic principles of design and self-organization can be applied to generate multifunctional electronic systems of complex, three-dimensional architecture.

Fibrinogen adsorption on polyurethanes with different surface-modifying end groups (SMEs) has been studied with sum-frequency-generation vibrational spectroscopy (SFG). The results show very different protein adsorption properties for different SMEs on the same backbone polymer. Fibrinogen binds weakly on the hydrophilic backbone of a poly(dimethyl siloxane) (PDMS)-modified polyurethane surface but leaves the hydrophobic PDMS part untouched. On sulfonate end-group-modified (SO(3(-) )) polyurethane surfaces, fibrinogen adsorbs well. However, on poly(ethylene oxide) (PEO)-modified surfaces, it adsorbs poorly. The protein-resistant character of PEO is probably due to steric repulsion. This work demonstrates the utility of SFG in the study of protein adsorption on polymeric biomaterials at the molecular level and the ability of SMEs to mediate protein adsorption.

We describe a method for repetitive and rapid formation of planar microarrays and gradients of proteins using patterned agarose stamps. It demonstrates: (i) micropatterning of agarose gels with feature sizes as small as 2 microm; (ii) inking of posts (diameter 50-1000 microm) on patterned agarose stamps with one or multiple (here, eight) proteins and repetitive stamping of patterns (>100 times in the case of one protein) and arrays (20 times in the case of eight proteins) without the need for intermediate re-inking; (iii) transferring spots of proteins with good homogeneity in surface coverage to glass slides; (iv) applying this technique to surface-based immunoassays; (v) stamping that requires only sub-nanomolar amounts of protein (typically approximately 3 microg in approximately 0.6 microL of solution); (vi) stamping without the need for drying of the proteins, as opposed to stamping with stamps made of poly(dimethylsiloxane); and (vii) patterning gradients of proteins by allowing two proteins to diffuse toward each other in an agarose stamp, followed by printing the protein gradients onto a surface.

This letter demonstrates the first utilization of surface tension based self-assembly on the 200 nm scale to form mechanically stable aggregates comprised of metallic rods. The self-assembly occurs as a result of the minimization of interfacial tension of liquid layers of a hydrophobic polymerizable adhesive that is precipitated on the rods. After the assembly, the adhesive is polymerized to form permanently bonded aggregates. Depending on the patterning of the rods and the chemical functionalization used, either closed 3D bundles or open 2D networks can be formed.

This paper describes the construction of three dimensional (3D) encapsulation devices in large numbers, using a novel self-assembling strategy characterized by high mechanical stability, controlled porosity, extreme miniaturization, high reproducibility and the possibility of integrating sensing and actuating electromechanical modules. We demonstrated encapsulation of microbeads and cells within the containers, thereby demonstrating one possible application in cell encapsulation therapy. Magnetic resonance (MR) images of the containers in fluidic media suggest radio frequency (RF) shielding and a susceptibility effect, providing characteristic hypointensity within the container, thereby allowing the containers to be easily detected. This demonstration is the first step toward the design of 3D, micropatterned, non-invasively trackable, encapsulation devices.

In numerous applications in microfluidics, cell growth, soft lithography, and molecular imprinting, the surface of poly(dimethylsiloxane) (PDMS) is modified from a hydrophobic methyl-terminated surface to a hydrophilic hydroxyl-terminated surface. In this study, we investigated molecular structural and orientational changes at the PDMS-air interface in response to three commonly used surface modification processes: exposure to long-wavelength ultraviolet light (UV), exposure to short-wavelength UV that generates ozone (UVO), and exposure to oxygen plasma (OP). The surfaces of two PDMS compositions (10:1 and 4:1 of base polymer/curing agent) were probed during modification, using monolayer-sensitive IR + visible sum frequency generation (SFG) vibrational spectroscopy, with two different polarization combinations. During PDMS surface modification, the peak intensities of CH3 side groups and CH2 cross-link groups decreased, while peak intensities of Si-OH groups increased. There was no significant change in the average orientation of the CH3 groups on the PDMS surface during modification. The concentration of CH3 groups on the surface decreased exponentially with time, for all three UV, UVO, and OP modification processes, with first order kinetics and time constants of approximately 160, 66, and 0.3 min, respectively. At steady state, residual CH3 groups were detected at the PDMS surface for UV and UVO treatments; however, there were negligible CH3 groups detected after OP modification.

In this communication, we report results obtained using surface-sensitive IR+Visible Sum Frequency Generation (SFG) nonlinear optical spectroscopy on interfaces of organic field effect transistors during operation. We observe remarkable correlations between trends in the surface vibrational spectra and electrical properties of the transistor, with changes in gate voltage (VG). These results suggest that field effects on electronic conduction in thin film organic semiconductor devices are correlated to interfacial nonlinear optical characteristics and point to the possibility of using SFG spectroscopy to monitor electronic properties of OFETs.

In this communication we describe a new chemical encapsulation and release platform using 3D microfabricated nanoliter scale containers with controlled porosity. The containers can be fabricated of magnetic materials that allow them to be remotely guided using magnetic fields. The favorable attributes of the containers that include a versatile highly parallel fabrication process, precisely engineered porosity, isotropic/anisotropic chemical release profiles, and remote magnetic guiding provide an attractive platform for engineering spatially controlled chemical reactions in microfluidic systems.

We demonstrate a new strategy to bond nanowires (NWs) using diffusion bonding of gold (Au). The strategy was used to form very large scale, electrically interconnected 3D NW networks composed of both homogeneous and heterogeneous (multisegmented) NWs. The size of the networks ranged from tens of micrometers to millimeters. We have measured the electrical characteristics of the networks and explored one application of the networks in 3D spatial chemical sensing.

We discuss finite element simulations and experiments involving the surface tension-driven self-folding of patterned polyhedra. Two-dimensional (2D) photolithographically patterned templates folded spontaneously when solder hinges between adjacent faces were liquefied. Minimization of interfacial free energy of the molten solder with the surrounding fluidic medium caused the solder to ball up, resulting in a torque that rotated adjacent faces and drove folding. The simulations indicate that the folding process can be precisely controlled, has fault tolerance, and can be used to fold polyhedra composed of a variety of materials, ranging in size from the millimeter scale down to the nanometer scale. Experimentally, we have folded metallic, arbitrarily patterned polyhedra ranging in size from 2 mm to 15 microm.

Several molecular therapies require the implantation of cells that secrete biotherapeutic molecules and imaging the location and microenvironment of the cellular implant to ascertain its function. We demonstrate noninvasive in vivo magnetic resonance imaging (MRI) of self-assembled microcontainers that are capable of cell encapsulation. Negative contrast was obtained to discern the microcontainer with MRI; positive contrast was obtained in the complete absence of background signal. MRI on a clinical scanner highlights the translational nature of this research. The microcontainers were loaded with cells that were dispersed in an extracellular matrix, and implanted both subcutaneously and in human tumor xenografts in SCID mice. MRI was performed on the implants, and microcontainers retrieved postimplantation showed cell viability both within and proximal to the implant. The microcontainers are characterized by their small size, three dimensionality, controlled porosity, ease of parallel fabrication, chemical and mechanical stability, and noninvasive traceability in vivo.

Lithographic patterning offers the possibility for precise structuring of drug delivery devices. The fabrication process can also facilitate the incorporation of advanced functionality for imaging, sensing, telemetry and actuation. However, a major limitation of present day lithographic fabrication is the inherent two-dimensionality of the patterning process. We review a new approach to construct three dimensional (3D) patterned containers by lithographically patterning two dimensional (2D) templates with liquefiable hinges that spontaneously fold upon heating into hollow polyhedral containers. The containers have finite encapsulation volumes, can be made small enough to pass through a hypodermic needle, and the 3D profile of the containers facilitates enhanced diffusion with the surrounding medium as compared to reservoir systems fabricated in planar substrates. We compare the features of the containers to those of present day drug delivery systems. These features include ease of manufacture, versatility in size and shape, monodisperse porosity, ability for spatial manipulation and remote triggering to release drugs on-demand, the incorporation of electronic modules, cell encapsulation, biocompatibility and stability. We also review possible applications in drug delivery and cell encapsulation therapy (CET). The results summarized in this review suggest a new strategy to enable construction of "smart", three dimensional drug delivery systems using lithography.

We devised cubic and pyramidal microcontainers for cell encapsulation. While the cube is easier to manipulate, the pyramid offers a higher surface area-to-volume ratio and may therefore provide the encapsulated cells with increased access to nutrients. To discern the microcontainers' implant location and environment, and to aid in image-guided therapy, we showed noninvasive detection of microcontainers using MRI. Diamagnetic microcontainers were imaged using the radio frequency (RF) shielding effect, with negative contrast localized to the interior of the microcontainers. For applications in which it is difficult to distinguish the microcontainers from other hypointensities, positive contrast can be used to discern them. We showed positive-contrast MRI of a diamagnetic microcontainer. To image microcontainers that are smaller than the spatial resolution of MRI, we performed in vivo negative-contrast MRI of a ferromagnetic microcontainer. As opposed to the diamagnetic microcontainer, the ferromagnetic microcontainer created a region of MRI contrast several times larger than the microcontainer's dimensions.

We investigated the solvent driven motion of lithographically structured poly- N-isopropylacrylamide (PNIPAm) gels. The gels were soaked in ethanol and then transferred to water, where they moved spontaneously. This movement was driven by the expulsion of the ethanol from the gel and subsequent ethanol spreading at the air-water interface. We utilized lithographic patterning of the gels at the micron-millimeter length scales to investigate the effect of size, shape and symmetry. Lithographic patterning allowed the structures to be fabricated in an identical manner, thereby allowing a single variable (such as shape, size, or symmetry) to be altered while minimizing change in other variables such as thickness, roughness and swelling characteristics. The diverse range of motions including translation, precession and rotation could be controlled and were recorded using videography. Gels were lithographically patterned with features less than 100 microm, and exhibited remarkably high linear and rotational velocities of up to 31 cm/s and 3529 rpm over time spans of seconds to minutes. We observed a reciprocal dependence of maximum rotational velocity on linear dimension. The linear velocity for all types of motion, along a line or curve, was analyzed and found to be similar across different shapes and sizes. This velocity was in the range of 17-39 cm/s even though our sizes and shapes varied across orders of magnitude. We postulate that this velocity is related to the velocity of spreading of ethanol on water, which is approximately 53 cm/s. Additionally, since this solvent powered motion is a clean, quiet and reusable source of motive power, with no need for on-board wiring or batteries, we explored applications in moving lithographically integrated metallic payloads on top of the gels and utilized the gels to move larger floating objects.

In this communication, we demonstrate the concept of single-use, chemically triggered, reversible tools in the form of mobile grippers that can be used to manipulate micro-objects. Both the closing and opening of the mobile grippers are triggered by chemicals, namely acetic acid (CH(3)COOH) and hydrogen peroxide (H(2)O(2)), respectively. The grippers close and open en masse based on chemically triggered, mechanical property changes within trilayer joints patterned within the gripper, and no external power is needed for operation. We describe the actuation of the gripper using a multilayer thin film model and demonstrate the utility of the gripper by picking-and-placing 200 microm diameter tubes and beads. Our pick-and-place microgripper is a first step toward the development of functional Micro Chemo-Mechanical Systems (MCMS), which are actuated by chemistry as opposed to electricity [as in Micro Electro-Mechanical Systems (MEMS)].

We describe the fabrication of 3D membranes with precisely patterned surface nanoporosity and their utilization in size selective sampling. The membranes were self-assembled as porous cubes from lithographically fabricated 2D templates (Leong et al., Langmuir 23:8747-8751, 2007) with face dimensions of 200 microm, volumes of 8 nL, and monodisperse pores ranging in size from approximately 10 microm to 100 nm. As opposed to conventional sampling and filtration schemes where fluid is moved across a static membrane, we demonstrate sampling by instead moving the 3D nanoporous membrane through the fluid. This new scheme allows for straightforward sampling in small volumes, with little to no loss. Membranes with five porous faces and one open face were moved through fluids to sample and retain nanoscale beads and cells based on pore size. Additionally, cells retained within the membranes were subsequently cultured and multiplied using standard cell culture protocols upon retrieval.

Proceedings of the National Academy of Sciences of the United States of America. Jan, 2009 | Pubmed ID: 19139411

We demonstrate mass-producible, tetherless microgrippers that can be remotely triggered by temperature and chemicals under biologically relevant conditions. The microgrippers use a self-contained actuation response, obviating the need for external tethers in operation. The grippers can be actuated en masse, even while spatially separated. We used the microgrippers to perform diverse functions, such as picking up a bead on a substrate and the removal of cells from tissue embedded at the end of a capillary (an in vitro biopsy).

Nature utilizes self-assembly to fabricate structures on length scales ranging from the atomic to the macro scale. Self-assembly has emerged as a paradigm in engineering that enables the highly parallel fabrication of complex, and often three-dimensional, structures from basic building blocks. Although there have been several demonstrations of this self-assembly fabrication process, rules that govern a priori design, yield and defect tolerance remain unknown. In this paper, we have designed the first model experimental system for systematically analyzing the influence of geometry on the self-assembly of 200 and 500 microm cubes and octahedra from tethered, multi-component, two-dimensional (2D) nets. We examined the self-assembly of all eleven 2D nets that can fold into cubes and octahedra, and we observed striking correlations between the compactness of the nets and the success of the assembly. Two measures of compactness were used for the nets: the number of vertex or topological connections and the radius of gyration. The success of the self-assembly process was determined by measuring the yield and classifying the defects. Our observation of increased self-assembly success with decreased radius of gyration and increased topological connectivity resembles theoretical models that describe the role of compactness in protein folding. Because of the differences in size and scale between our system and the protein folding system, we postulate that this hypothesis may be more universal to self-assembling systems in general. Apart from being intellectually intriguing, the findings could enable the assembly of more complicated polyhedral structures (e.g. dodecahedra) by allowing a priori selection of a net that might self-assemble with high yields.

The construction of three-dimensional (3D) objects, with any desired surface patterns, is both critical to and easily achieved in macroscale science and engineering. However, on the nanoscale, 3D fabrication is limited to particles with only very limited surface patterning. Here, we demonstrate a self-assembly strategy that harnesses the strengths of well-established 2D nanoscale patterning techniques and additionally enables the construction of stable 3D polyhedral nanoparticles. As a proof of the concept, we self-assembled cubic particles with sizes as small as 100 nm and with specific and lithographically defined surface patterns.

Microassembly based on origami, the Japanese art of paper folding, presents an attractive methodology for constructing complex three-dimensional (3D) devices and advanced materials. A variety of functional structures have been created using patterned metallic, semiconducting, and polymeric thin films, but have been limited to those that curve in a single direction. We report a design framework that can be used to achieve spontaneous bidirectional folds with any desired angle, and we demonstrate theoretical and experimental realizations of complex 3D structures with +90 degrees , -90 degrees , +180 degrees , and -180 degrees folds. The strategy is parallel, versatile, and compatible with conventional microfabrication.

The concept of self-assembly of a two-dimensional (2D) template to a three-dimensional (3D) structure has been suggested as a strategy to enable highly parallel fabrication of complex, patterned microstructures. We have previously studied the surface tension based self-assembly of patterned, microscale polyhedral containers (cubes, square pyramids and tetrahedral frusta). In this paper, we describe the observed hierarchical self-assembly of more complex, patterned polyhedral containers in the form of regular dodecahedra and octahedra. The hierarchical design methodology, combined with the use of self-correction mechanisms, was found to greatly reduce the propagation of self-assembly error that occurs in these more complex systems. It is a highly effective way to mass-produce patterned, complex 3D structures on the microscale and could also facilitate encapsulation of cargo in a parallel and cost-effective manner. Furthermore, the behavior that we have observed may be useful in the assembly of complex systems with large numbers of components.

We describe a strategy to construct three-dimensional (3D) containers with nanoporous walls by the self-assembly of lithographically patterned two-dimensional cruciforms with solder hinges. The first step involves fabricating two-dimensional (2D) cruciforms composed of six unlinked patterns: each pattern has an open window. The second step entails photolithographic patterning of solder hinges that connect the cruciform. The third step involves the deposition of polystyrene particles within the windows and the subsequent electrodeposition of metal in the voids between the polystyrene particles. Following the dissolution of the particles, the cruciforms are released from the substrate and heated above the melting point of the solder causing the cruciforms to spontaneously fold up into 3D cubic containers with nanoporous walls. We believe these 3D containers with nanoporous side walls are promising for molecular separations and cell-based therapies.

We describe the use of conventional photolithography to construct three dimensional (3D) thin film scaffolds and direct the growth of fibroblasts into three distinct and anatomically relevant geometries: cylinders, spirals and bi-directionally folded sheets. The scaffolds were micropatterned as two dimensional sheets which then spontaneously assembled into specific geometries upon release from the underlying substrate. The viability of fibroblasts cultured on these self-assembling scaffolds was verified using fluorescence microscopy; cell morphology and spreading were studied using scanning electron microscopy. We demonstrate control over scaffold size, radius of curvature and folding pitch, thereby enabling an attractive approach for investigating the effects of these 3D geometric factors on cell behaviour.

Despite the fact that we live in a 3D world and macroscale engineering is 3D, conventional submillimeter-scale engineering is inherently 2D. New fabrication and patterning strategies are needed to enable truly 3D-engineered structures at small size scales. Here, strategies that have been developed over the past two decades that seek to enable such millimeter to nanoscale 3D fabrication and patterning are reviewed. A focus is the strategy of self-assembly, specifically in a biologically inspired, more deterministic form, known as self-folding. Self-folding methods can leverage the strengths of lithography to enable the construction of precisely patterned 3D structures and "smart" components. This self-assembly approach is compared with other 3D fabrication paradigms, and its advantages and disadvantages are discussed.

We describe strategies to curve, rotate, align, and bond precisely patterned two-dimensional (2D) nanoscale panels using forces derived from a minimization of surface area of liquefying or coalescing metallic grains. We demonstrate the utility of this approach by discussing variations in template size, patterns, and material composition. The strategy provides a solution path to overcome the limitation of inherently 2D lithographic processes by transforming 2D templates into mechanically robust and precisely patterned nanoscale curved structures and polyhedra with considerable versatility in material composition.

This article investigates the three-dimensional self-assembly of submillimeter scale polyhedra using surface forces. Using a combination of energy landscape calculations and experiments, we investigate the influence of patterns of hydrophobic surfaces on generating defect-free, closed-packed aggregates of polyhedra, with a focus on cubic units. Calculations show that surface patterning strongly affects the interaction between individual units as well as that of the unit with the growing assembly. As expected, an increase in the hydrophobic surface area on each face results in larger global minima. However, it is the distribution of hydrophobic surface area on each cubic face that is strongly correlated to the energetic parameters driving low-defect assembly. For patterns with the same overall area, minimizing the radius of gyration and maximizing the angular distribution leads to steep energy curves, with a lower propensity for entrapment in metastable states. Experimentally, 200-500 microm sized metallic polyhedra were fabricated using a self-folding process, and the exposed surfaces were coated with a hydrophobic polymer. Cubes with surface patterns were agitated to cause aggregative self-assembly. Experimental results were consistent with energy calculations and suggest that geometric patterns with large overall areas, low radii of gyration, and high angular distributions result in efficient and low-defect assembly.

We demonstrate a methodology that utilizes the specificity of enzyme-substrate biomolecular interactions to trigger miniaturized tools under biocompatible conditions. Miniaturized grippers were constructed using multilayer hinges that employed intrinsic strain energy and biopolymer triggers, as well as ferromagnetic elements. This composition obviated the need for external energy sources and allowed for remote manipulation of the tools. Selective enzymatic degradation of biopolymer hinge components triggered closing of the grippers; subsequent reopening was achieved with an orthogonal enzyme. We highlight the utility of these enzymatically triggered tools by demonstrating the biopsy of liver tissue from a model organ system and gripping and releasing an alginate bead. This strategy suggests an approach for the development of smart materials and devices that autonomously reconfigure in response to extremely specific biological environments.

Gold (Au) nanoparticles (NPs) have large surface areas and novel optical properties and can be readily functionalized using thiol-based chemistry; hence, they are useful in bioanalytical chemistry. Here, we describe a one-step, plasma-etching process that results in the spontaneous formation of Au NP coated recessed microstructures in silicon (Si). Mechanistically, the plasma etch rate of Si was enhanced in the vicinity of 10-100 nm thick Au patterns resulting in the formation of microwells or microchannels uniformly coated with 20-30 nm sized Au NPs. The methodology provides versatility in the types of microstructures that can be formed by varying the shape and dimensions of the Au patterns and the etch time. We also describe selective binding of antibodies to Au NP coated Si microwells using thiol-based surface modification.

We describe the spontaneous wrinkling, saddling, and wedging of metallic, annular bilayer nanostructures driven by grain coalescence in one of the layers. Experiments revealed these different outcomes based on the dimensions of the annuli, and we find that the essential features are captured using finite element simulations of the plastic deformation in the metal bilayers. Our results show that the dimensions and nanomechanics associated with the plastic deformation of planar nanostructures can be important in forming complex three-dimensional nanostructures.

We demonstrate self-folding of precisely patterned, optically transparent, all-polymeric containers and describe their utility in mammalian cell and microorganism encapsulation and culture. The polyhedral containers, with SU-8 faces and biodegradable polycaprolactone (PCL) hinges, spontaneously assembled on heating. Self-folding was driven by a minimization of surface area of the liquefying PCL hinges within lithographically patterned two-dimensional (2D) templates. The strategy allowed for the fabrication of containers with variable polyhedral shapes, sizes and precisely defined porosities in all three dimensions. We provide proof-of-concept for the use of these polymeric containers as encapsulants for beads, chemicals, mammalian cells and bacteria. We also compare accelerated hinge degradation rates in alkaline solutions of varying pH. These optically transparent containers resemble three-dimensional (3D) micro-Petri dishes and can be utilized to sustain, monitor and deliver living biological components.

We propose the concept of three-dimensional (3D) microwell arrays for cell culture applications and highlight the importance of oxygen diffusion through pores in all three dimensions to enhance cell viability.

We describe an assembly technique useful for generating ordered arrays of nanowires (NWs) between electrodes via dielectrophoresis (DEP) and an analysis technique useful for extracting quantitative information about the local electric fields and dielectrophoretic forces from video microscopy data. By tuning the magnitude of the applied electric fields such that the attractive forces on the NWs are of the same order of magnitude as the Brownian forces, and by taking advantage of the inter-NW repulsive forces during DEP, NWs can be assembled into parallel arrays with high reproducibility. By employing a particle-tracking code and analysis of NW motion, we demonstrate a method for quantitative mapping of the dielectrophoretic torques and NW-surface interactions as a function of position on the substrate, which allows a more complete understanding of the dynamics of the assembly and the ability to control these parameters for precise assembly.

Cell encapsulation therapy (CET) provides an attractive means to transplant cells without the need for immunosuppression. The cells are immunoisolated by surrounding them with a synthetic, semipermeable nanoporous membrane that allows selective permeation of nutrients and therapeutics while isolating the cells from hostile immune components. This communication describes the fabrication and in vitro characterization of lithographically structured and self-folded containers for immunoprotective cell encapsulation. Lithographic patterning ensured identical shapes, sizes, tunable porosity, and precise volumetric control, whereas self-folding enabled transformation of two-dimensional porous membranes into cubes, ensuring that pores were present in all three dimensions for adequate diffusion of O(2) and other nutrients to encapsulated cells. We fabricated containers with varying pore sizes and observed that pores sizes of approximately 78 nm were sufficient to significantly inhibit diffusion of IgG (the smallest antibody) and permit adequate diffusion of insulin, highlighting the possibility to utilize these containers to develop a lithographically structured bioartificial pancreas. FROM THE CLINICAL EDITOR: In this paper, a novel immunoisolation technique is presented to enable cell transplant survival by surrounding them with a synthetic, semipermeable nanoporous membrane that allows selective permeation of nutrients and therapeutics while isolating the cells from hostile immune components. This method may pave the way to effective pancreatic islet cell transplantation.

An important feature of naturally self-assembled systems such as leaves and tissues is that they are curved and have embedded fluidic channels that enable the transport of nutrients to, or removal of waste from, specific three-dimensional regions. Here we report the self-assembly of photopatterned polymers, and consequently microfluidic devices, into curved geometries. We discover that differentially photo-crosslinked SU-8 films spontaneously and reversibly curve on film de-solvation and re-solvation. Photolithographic patterning of the SU-8 films enables the self-assembly of cylinders, cubes and bidirectionally folded sheets. We integrate polydimethylsiloxane microfluidic channels with these SU-8 films to self-assemble curved microfluidic networks.

Proceedings of the National Academy of Sciences of the United States of America. Dec, 2011 | Pubmed ID: 22139373

Self-assembly has emerged as a paradigm for highly parallel fabrication of complex three-dimensional structures. However, there are few principles that guide a priori design, yield, and defect tolerance of self-assembling structures. We examine with experiment and theory the geometric principles that underlie self-folding of submillimeter-scale higher polyhedra from two-dimensional nets. In particular, we computationally search for nets within a large set of possibilities and then test these nets experimentally. Our main findings are that (i) compactness is a simple and effective design principle for maximizing the yield of self-folding polyhedra; and (ii) shortest paths from 2D nets to 3D polyhedra in the configuration space are important for rationalizing experimentally observed folding pathways. Our work provides a model problem amenable to experimental and theoretical analysis of design principles and pathways in self-assembly.

Because the native cellular environment is 3D, there is a need to extend planar, micro- and nanostructured biomedical devices to the third dimension. Self-folding methods can extend the precision of planar lithographic patterning into the third dimension and create reconfigurable structures that fold or unfold in response to specific environmental cues. Here, we review the use of hinge-based self-folding methods in the creation of functional 3D biomedical devices including precisely patterned nano- to centimeter scale polyhedral containers, scaffolds for cell culture and reconfigurable surgical tools such as grippers that respond autonomously to specific chemicals.

We describe nanoscale tools in the form of autonomous and remotely guided catalytically self-propelled InGaAs/GaAs/(Cr)Pt tubes. These rolled-up tubes with diameters in the range of 280-600 nm move in hydrogen peroxide solutions with speeds as high as 180 Î¼m s(-1). The effective transfer of chemical energy to translational motion has allowed these tubes to perform useful tasks such as transport of cargo. Furthermore, we observed that, while cylindrically rolled-up tubes move in a straight line, asymmetrically rolled-up tubes move in a corkscrew-like trajectory, allowing these tubes to drill and embed themselves into biomaterials. Our observations suggest that shape and asymmetry can be utilized to direct the motion of catalytic nanotubes and enable mechanized functions at the nanoscale.

Self-folding broadly refers to self-assembly processes wherein thin films or interconnected planar templates curve, roll-up or fold into three dimensional (3D) structures such as cylindrical tubes, spirals, corrugated sheets or polyhedra. The process has been demonstrated with metallic, semiconducting and polymeric films and has been used to curve tubes with diameters as small as 2nm and fold polyhedra as small as 100nm, with a surface patterning resolution of 15nm. Self-folding methods are important for drug delivery applications since they provide a means to realize 3D, biocompatible, all-polymeric containers with well-tailored composition, size, shape, wall thickness, porosity, surface patterns and chemistry. Self-folding is also a highly parallel process, and it is possible to encapsulate or self-load therapeutic cargo during assembly. A variety of therapeutic cargos such as small molecules, peptides, proteins, bacteria, fungi and mammalian cells have been encapsulated in self-folded polymeric containers. In this review, we focus on self-folding of all-polymeric containers. We discuss the mechanistic aspects of self-folding of polymeric containers driven by differential stresses or surface tension forces, the applications of self-folding polymers in drug delivery and we outline future challenges.

Nanopores with conical geometries have been found to rectify ionic current in electrolytes. While nanopores in semiconducting membranes are known to modulate ionic transport through gated modification of pore surface charge, the fabrication of conical nanopores in silicon (Si) has proven challenging. Here, we report the discovery that gold (Au) nanoparticle (NP)-assisted plasma etching results in the formation of conical etch profiles in Si. These conical profiles result due to enhanced Si etch rates in the vicinity of the Au NPs. We show that this process provides a convenient and versatile means to fabricate conical nanopores in Si membranes and crystals with variable pore-diameters and cone-angles. We investigated ionic transport through these pores and observed that rectification ratios could be enhanced by a factor of over 100 by voltage gating alone, and that these pores could function as ionic switches with high on-off ratios of approximately 260. Further, we demonstrate voltage gated control over protein transport, which is of importance in lab-on-a-chip devices and biomolecular separations.

Spatial control of chemical reactions, with micro- and nanometer scale resolution, has important consequences for one pot synthesis, engineering complex reactions, developmental biology, cellular biochemistry and emergent behavior. We review synthetic methods to engineer this spatial control using chemical diffusion from spherical particles, shells and polyhedra. We discuss systems that enable both isotropic and anisotropic chemical release from isolated and arrayed particles to create inhomogeneous and spatially patterned chemical fields. In addition to such finite chemical sources, we also discuss spatial control enabled with laminar flow in 2D and 3D microfluidic networks. Throughout the paper, we highlight applications of spatially controlled chemistry in chemical kinetics, reaction-diffusion systems, chemotaxis and morphogenesis.

Self-folded magnetic microtools with sharp ends are directed at enabling drilling and related incision operations of tissues, ex vivo, in a fluid with a viscosity similar to that of blood. These microtools change their rotation from a horizontal to a vertical one when they are immersed into a rotational magnetic field. Novel self-assembly paradigms with magnetic materials can enable the creation of remotely controlled and mass-produced tools for potential applications in minimally invasive surgery.

Thermally activated, untethered microgrippers can reach narrow conduits in the body and be used to excise tissue for diagnostic analyses. As depicted in the figure, the feasibility of an in vivo biopsy of the porcine bile duct using untethered microgrippers is demonstrated.

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